Exosomes derived from pioglitazone-pretreated MSCs accelerate diabetic wound healing through enhancing angiogenesis

被引：282

作者：

Hu, Yiqiang ^{[1
,2
]}

Tao, Ranyang ^{[1
,2
]}

Chen, Lang ^{[1
,2
]}

Xiong, Yuan ^{[1
,2
]}

Xue, Hang ^{[1
,2
]}

Hu, Liangcong ^{[1
,2
]}

Yan, Chenchen ^{[1
,2
]}

Xie, Xudong ^{[1
,2
]}

Lin, Ze ^{[1
,2
]}

Panayi, Adriana C. ^{[3
]}

Mi, Bobin ^{[1
,2
]}

Liu, Guohui ^{[1
,2
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Orthopaed, Wuhan 430022, Peoples R China

[2] Hubei Prov Key Lab Oral & Maxillofacial Dev & Reg, Wuhan 430022, Peoples R China

[3] Harvard Med Sch, Brigham & Womens Hosp, Dept Plast Surg, Boston, MA 02215 USA

来源：

JOURNAL OF NANOBIOTECHNOLOGY | 2021年 / 19卷 / 01期

基金：

美国国家科学基金会;

关键词：

Exosomes; Mesenchymal stem cells; Pioglitazone; Diabetic wound; Angiogenesis; MESENCHYMAL STEM-CELLS; BONE-MARROW; REGENERATION;

D O I：

10.1186/s12951-021-00894-5

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 [微生物学]; 090105 [作物生产系统与生态工程];

摘要：

Background: Enhanced angiogenesis can promote diabetic wound healing. Mesenchymal stem cells (MSCs)-derived exosomes, which are cell-free therapeutics, are promising candidates for the treatment of diabetic wound healing. The present study aimed to investigate the effect of exosomes derived from MSCs pretreated with pioglitazone (PGZ-Exos) on diabetic wound healing. Results: We isolated PGZ-Exos from the supernatants of pioglitazone-treated BMSCs and found that PGZ-Exos significantly promote the cell viability and proliferation of Human Umbilical Vein Vascular Endothelial Cells (HUVECs) injured by high glucose (HG). PGZ-Exos enhanced the biological functions of HUVECs, including migration, tube formation, wound repair and VEGF expression in vitro. In addition, PGZ-Exos promoted the protein expression of p-AKT, p-PI3K and p-eNOS and suppressed that of PTEN. LY294002 inhibited the biological function of HUVECs through inhibition of the PI3K/AKT/eNOS pathway. In vivo modeling in diabetic rat wounds showed that pioglitazone pretreatment enhanced the therapeutic efficacy of MSCs-derived exosomes and accelerated diabetic wound healing via enhanced angiogenesis. In addition, PGZ-Exos promoted collagen deposition, ECM remodeling and VEGF and CD31 expression, indicating adequate angiogenesis in diabetic wound healing. Conclusions: PGZ-Exos accelerated diabetic wound healing by promoting the angiogenic function of HUVECs through activation of the PI3K/AKT/eNOS pathway. This offers a promising novel cell-free therapy for treating diabetic wound healing.

引用

页数：17

共 60 条

[1]

Mesenchymal Stromal Cell-Derived Extracellular Vesicles in the Treatment of Diabetic Foot Ulcers: Application and Challenges [J].